The sympathetic nervous system (SNS) plays an important role in the regulation of blood pressure. Our research program involves the development of biochemical tests of the status and function of the SNS in man, and the application of these tests to studies of a possible role of the SNS in hypertension and other diseases. Special emphasis is placed on the importance of genetic factors in the determination of individual differences in the activities of catecholamine biosynthetic and degradative enzymes. Our previous studies of serum dopamine-beta-hydroxylase (DBH) and erythrocyte catechol-O-methyltransferase (COMT) activities have demonstrated the autosomal recessive inheritance of low activities of these enzymes in man. We now propose to expand these studies to include two additional catecholamine metabolic enzymes, monoamine oxidase (MAO) and phenol sulphotransferase (PST). Inhibitors of MAO have been used clinically as antihypertensive agents. PST plays an important role in the metabolism of catecholamines in the central nervous system and in the metabolism of drugs used in the treatment of hypertension and other cardiovascular diseases. Special emphasis will be placed on a possible role of inheritance in the determination of individual variations in these enzyme activities. It will be systematically determined whether the biochemical properties of MAO and PST in human blood are similar to those of the enzymes in other tissues, and whether individual variations in MAO and PST activities play a role in individual variations in adrenergic function and metabolism of drugs related to catecholamines. These studies represent an additional step in our attempt to systematically evaluate the possible role of individual variations in catecholamine metabolic enzymes in the pathogenesis of disease such as hypertension and in the responses of individual patients to drugs metabolized by these enzymes.